Arrowhead Pharmaceuticals (NASDAQ:ARWR) executives outlined early clinical data for its RNA interference dimer program, progress in the launch of plozasiran and plans for central nervous system and metabolic disease candidates during the Morgan Stanley Global Healthcare Conference.
Early Dimer Data Points to Dual-Target Approach
Chief Executive Officer Chris Anzalone said the company’s ARO-DIMER-PA candidate represented the first demonstration of knockdown of two genes with a single RNAi molecule. The program is designed for patients with mixed hyperlipidemia, a population Arrowhead estimated at about 20 million people in the U.S. with elevated LDL cholesterol and triglycerides.
The disclosed results were from single-dose cohorts, Hamilton said. The study is fully enrolled, and the company expects to present multidose data at a future medical conference, potentially in the fourth quarter. Arrowhead is evaluating quarterly dosing and will assess whether dosing can be extended to every six months.
The company plans to amend the current study to add a multidose portion in mixed-hyperlipidemia patients before proceeding to a Phase III study using LDL reduction as the primary endpoint. Anzalone said Arrowhead hopes to pursue a regulatory path based on LDL reduction while conducting a longer-term cardiovascular outcomes trial.
Arrowhead is also developing additional dimer programs in cardiovascular disease, obesity and metabolic dysfunction-associated steatohepatitis, or MASH. Anzalone said the company expects to provide further details on certain additional dimer candidates in 2027.
Plozasiran Launch and SHTG Expansion Plans
Anzalone said the commercial launch of plozasiran in familial chylomicronemia syndrome, or FCS, has been smooth and somewhat faster than anticipated. He said Arrowhead has found more clinical FCS patients than initially expected, has expanded its sales force, and has secured coverage policies from most payers in FCS.
The company is now focused on seeking approval in severe hypertriglyceridemia, or SHTG. Arrowhead acquired a priority review voucher to accelerate the review process, according to Anzalone.
Hamilton summarized results from the SHASTA-3 and SHASTA-4 studies, reporting triglyceride reductions of 80% from baseline. He said those reductions were associated with statistically significant reductions in acute pancreatitis event rates and improvements in time to event. The studies also showed more patients reaching triglyceride levels below 150 and below 500, he said.
Hamilton said pooled safety data showed no signs of hypersensitivity, anaphylactoid reactions or thrombocytopenia. He also described the liver safety profile as “pretty quiet,” citing no statistically significant difference between active treatment and placebo in liver-fat changes and placebo-like transaminase changes.
Anzalone said Arrowhead estimates there are approximately 3.5 million people with triglyceride levels above 500. He characterized the drug’s positioning as centered on reducing pancreatitis risk rather than cardiovascular risk. Arrowhead’s current net price is $45,000 annually, which Anzalone said the company views as appropriate given the cost and severity of pancreatitis.
He said the company’s initial commercial emphasis in SHTG will be on reaching untreated patients rather than switching patients from competing therapies. Anzalone cautioned that the launch may develop gradually over two to three years because physicians and patients need education on treating elevated triglycerides.
Pipeline Focus Includes Tau, MASH and Obesity
Hamilton said ARO-MAPT is designed to silence the MAPT gene, which encodes tau protein. Misfolded tau is associated with Alzheimer’s disease and other tauopathies, including progressive supranuclear palsy and certain forms of frontotemporal dementia.
Unlike an existing antisense oligonucleotide approach delivered intrathecally through lumbar puncture, Arrowhead’s candidate is administered subcutaneously and uses a Fab fragment targeting the transferrin receptor to cross the blood-brain barrier. Hamilton said animal studies suggest the approach may provide more homogeneous distribution across brain regions.
Arrowhead expects initial human data for ARO-MAPT at the end of the month or in early October. Hamilton said the company views a 50% to 60% reduction in total cerebrospinal fluid tau as an important threshold, though the ongoing dose-escalation study is intended to determine doses for later-stage development.
In metabolic disease, Arrowhead is advancing ARO-INHBE and ARO-ALK7, which target different parts of a liver-to-adipocyte signaling pathway involved in fat storage. Hamilton said ARO-INHBE is further advanced and is entering a Phase II study focused primarily on MASH, including biopsy-based endpoints, liver fat and body-composition measures. Additional data for both programs are expected toward year-end.
Executives also said the company uses artificial intelligence in target discovery, ligand design and sequence selection, while continuing to build internal AI capabilities.
About Arrowhead Pharmaceuticals (NASDAQ:ARWR)
Arrowhead Pharmaceuticals, Inc (NASDAQ:ARWR) is a biopharmaceutical company focused on developing medicines that silence disease-causing genes. The company uses RNA interference (RNAi), a biological process that reduces the production of specific proteins, to target conditions that may be difficult to treat with conventional drugs.
Arrowhead’s proprietary TRiM platform is designed to deliver RNAi-based therapies to different tissues, including the liver, lungs and other organs. Its investigational pipeline has included candidates for cardiovascular and metabolic diseases, liver disorders, pulmonary conditions and inflammatory diseases.
